lecture 76: Basics of Cell signaling and receptors

What is the main function of cell signaling?

To coordinate intercellular communication, maintain tissue homeostasis, and respond to environmental stimuli.

What are the three major ways cells communicate?

1. Direct physical contact, 2. Soluble chemical signals, 3. Environmental stimuli (light, temperature, etc.).

What are common types of chemical signals?

Proteins, peptides, catecholamines, steroids, gases (NO, CO, H₂S), cytokines, and hormones.

What determines whether a cell responds to a signal molecule?

Presence of a specific receptor and the integrity of downstream signaling components.

What are the two main categories of signaling distance?

Local (autocrine, paracrine, neuronal) and long-distance (endocrine).

What is autocrine signaling?

The cell releases signaling molecules that act on itself.

What is intracrine signaling?

Signaling molecules act within the same cell without being secreted.

What is paracrine signaling?

Signals act on nearby cells within a localized environment.

What is endocrine signaling?

Hormones travel through the bloodstream to act on distant target cells

What is the most “public” form of cell signaling?

Endocrine signaling

What are extracellular vesicles (EVs)?

Membrane-bound vesicles that carry bioactive molecules, receptors, mRNA, or even mitochondria between cells.

What characterizes a “fast” cellular response?

Uses pre-existing proteins; examples include vision, saliva secretion, and the fight-or-flight response.

What characterizes a “slow” cellular response?

Requires gene transcription and protein synthesis, such as cell growth and differentiation.

What are the three general stages of signal transduction?

Reception → Transduction → Response.

What defines a receptor in cell signaling?

A protein that specifically binds a ligand (agonist or antagonist) and initiates a response.

What is an agonist?

A molecule that binds to and activates a receptor.

What is an antagonist?

A molecule that binds to a receptor but blocks activation.

 Where are plasma membrane receptors located?

Spanning the cell membrane, interacting with water-soluble ligands.

Name the three major classes of membrane receptors.

1. Ion channel–linked receptors, 2. G-protein–coupled receptors (GPCRs), 3. Enzyme-linked receptors.

What is the function of cell membrane receptor pathways?

They modulate cytoplasmic and nuclear processes — “fast” non-nuclear or “slow” nuclear signaling.

What molecules activate intracellular receptors?

Small or hydrophobic ligands such as steroids, thyroid hormones (T₃/T₄), vitamin D, retinoids, and nitric oxide.

How do intracellular receptors affect gene expression?

Ligand-receptor complexes bind DNA to alter transcription of specific genes

What are the key properties of receptor signaling cascades?

Specificity, sensitivity, amplification, spillover, isoforms, down-regulation, up-regulation, and cross-talk.

What confers specificity in signaling?

Structural complementarity between ligand and receptor (“lock and key”).

Can one signal molecule produce different effects in different tissues?

Yes, depending on receptor subtype and downstream pathways.

What is an example of receptor specificity in adrenergic signaling?

Epinephrine causes vasodilation via β₂ receptors in skeletal muscle and vasoconstriction via α receptors in intestine.

What determines receptor sensitivity?

Binding affinity (Kᴅ) and receptor number on the target cell.

What is the Kᴅ (dissociation constant)?

The ligand concentration required to occupy half of the receptors — inversely related to affinity.

How do hormone and neurotransmitter receptors differ in affinity?

Hormone receptors have high affinity (nM–pM) and slow off-rate; neurotransmitter receptors have low affinity (µM) and fast off-rate.

What are spare receptors?

Extra receptors that allow maximal response even when not all are occupied.

What advantages do spare receptors provide?

Greater sensitivity and faster response at low ligand concentrations.

What is a clinical example of spare receptors?

β-adrenergic receptors in cardiac myocytes allow high responsiveness to catecholamines.

How does insulin exhibit spare receptor behavior?

Low concentrations → glucose uptake; high concentrations → growth factor signaling (tumor risk in T2DM).

What is signal amplification?

A cascade where a few activated receptors produce a greatly magnified cellular response.

How strong can amplification be?

Up to 10¹²-fold.

What hormone exemplifies massive signal amplification?

Epinephrine — one molecule can trigger large metabolic changes.

What is hormone spillover?

When one hormone binds and activates a receptor of a different hormone.

What is an example of hormone spillover?

Insulin can bind to IGF-1 receptors and vice versa.

What are receptor isoforms?

Multiple receptor forms for the same ligand with different sensitivities and effects.

What is receptor down-regulation?

Decrease in receptor number or sensitivity after chronic agonist exposure.

What is the physiological role of down-regulation?

Prevents overstimulation and maintains homeostasis.

What is an examples of down-regulation in disease or drugs?

Insulin receptors in Type 2 diabetes, opioid receptor tolerance, nicotinic receptor desensitization in smokers.

What is receptor up-regulation?

Increase in receptor number or signaling proteins after signal withdrawal or antagonist exposure.

What is the physiological purpose of up-regulation?

Restores sensitivity to a reduced signal through compensatory feedback.

What is an examples of up-regulation?

β-blocker withdrawal (cardiac β-receptor increase), TSH receptor increase in hypothyroidism, dopamine receptor increase with antipsychotics.

What is cross-talk in signaling pathways?

Interaction between distinct pathways that allows coordinated cellular responses.

Why is cross-talk important?

It allows the cell to integrate multiple signals simultaneously for balanced regulation.

Why does abrupt withdrawal from β-blockers cause rebound tachycardia?

Because of up-regulated β-adrenergic receptors during chronic blockade.

Why can insulin act as a growth factor in hyperinsulinemia?

Hormone spillover and activation of IGF-1 receptors at high concentrations.

What term describes decreased receptor responsiveness from chronic stimulation?

Tachyphylaxis (or desensitization)